HDL subclass proteomic analysis and functional implication of protein dynamic change during HDL maturation

Yuling Zhang, Scott M. Gordon, Hang Xi, Seungbum Choi, Merlin Abner Paz, Runlu Sun, William Yang, Jason Saredy, Mohsin Khan, Alan Thomas Remaley, Jing Feng Wang, Xiaofeng Yang, Hong Wang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

Recent clinical trials reported that increasing high-density lipoprotein-cholesterol (HDL-C)levels does not improve cardiovascular outcomes. We hypothesize that HDL proteome dynamics determine HDL cardioprotective functions. In this study, we characterized proteome profiles in HDL subclasses and established their functional connection. Mouse plasma was fractionized by fast protein liquid chromatography, examined for protein, cholesterial, phospholipid and trigliceride content. Small, medium and large (S/M/L)-HDL subclasseses were collected for proteomic analysis by mass spectrometry. Fifty-one HDL proteins (39 in S-HDL, 27 in M-HDL and 29 in L-HDL)were identified and grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). Eleven HDL common proteins were identified in all HDL subclasses. Sixteen, 3 and 7 proteins were found only in S-HDL, M-HDL and L-HDL, respectively. We established HDL protein dynamic distribution in S/M/L-HDL and developed a model of protein composition change during HDL maturation. We found that cholesterol efflux and immune response are essential functions for all HDL particles, and amino acid metabolism is a special function of S-HDL, whereas anti-coagulation is special for M-HDL. Pon1 is recruited into M/L-HDL to provide its antioxidative function. ApoE is incorporated into L-HDL to optimize its cholesterial clearance function. Next, we acquired HDL proteome data from Pubmed and identified 12 replicated proteins in human and mouse HDL particle. Finally, we extracted 3 shared top moleccular pathways (LXR/RXR, FXR/RXR and acute phase response)for all HDL particles and 5 top disease/bio-functions differentially related to S/M/L-HDL subclasses, and presented one top net works for each HDL subclass. We conclude that beside their essencial functions of cholesterol efflux and immune response, HDL aquired antioxidative and cholesterol clearance functions by recruiting Pon1 and ApoE during HDL maturation.

Original languageEnglish
Article number101222
JournalRedox Biology
Volume24
DOIs
StatePublished - Jun 2019

Bibliographical note

Funding Information:
This work was supported in part by the National Institutes of Health grants HL67033 , HL77288 , HL82774 , HL-110764 , HL130233 , HL131460 , DK104114 , DK113775 to HW and HL131460 to HW/EC/XFY . YLZ is supported by a fellowship from China Scholarship Council .

Publisher Copyright:
© 2019 The Authors

Keywords

  • Cardiovascular disease
  • Lipids and cholesterol
  • Metabolism
  • Proteomics
  • Risk factors

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

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